Journal of Clinical & Experimental Dermatology Research
Open Access

Verrucous Psoriasis: An Integrative Review of Pathogenesis, Diagnosis, and Treatment Landscape

Zhixuan Guo, Menger Guo, Guangji Gui, Yuhua Liu and Xiangyun Li^{* *}Correspondence: Xiangyun Li, Department of Dermatology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China, Email:

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Introduction

Verrucous Psoriasis (VP), a rare and intriguing subset of psoriasis, is distinguished by its hyperkeratotic, warty lesions that can masquerade as other dermatological conditions, including verruca vulgaris, squamous cell carcinoma, hypertrophic lichen planus and other conditions. The histopathological features of VP, which include acanthosis, papillomatosis, and hyperkeratosis, overlap with those of common warts, complicating the diagnostic process. Furthermore, the response of VP to traditional psoriasis therapies has been inconsistent, with some cases showing resistance to topical medications, phototherapy, systemic agents, and even biologics. Due to the rarity of VP, knowledge of its pathophysiology, clinical and histopathological presentation, and optimal management strategies has been limited. Our review of the literature aims to provide a synthesis of the current understanding of this rare condition.

Literature Review

VP is a rare and complex variant of psoriasis which typically presents with symmetric, hypertrophic, and verrucous plaques, often localized on the extremities (Table 1). However, it can range from localized to extensive involvement, with a higher prevalence in middle-aged and elderly males. Notably, VP can manifest unilaterally, or following surgical trauma, as illustrated in a case post-coronary artery bypass surgery [1,2]. Although a small percentage of patients are newly diagnosed, most of the verrucous psoriasis have a previous history of psoriasis vulgaris (Table S1). Besides the erythematosquamous plaques, the wart-like appearance of VP often leads to misdiagnosis with conditions like verruca vulgaris, squamous cell carcinoma, hypertrophic lichen planus and other skin diseases. In addition to the usual presentation, VP can also present with erythrodermic lesions [3-5]. The diversity of clinical manifestations makes further laboratory tests particularly important.

Table 1: Clinical, histopathologic features and treatments of VP.

Histopathologic examination of VP lesions reveals a spectrum of features that, while overlapping with classic psoriasis, also exhibit unique characteristics [6,7]. The epidermis in VP demonstrates psoriasiform hyperplasia, with elongated and tortuous rete ridges, creating a papillomatous surface. This is accompanied by marked parakeratosis and hyperkeratosis, resulting in the formation of the thick scale that is a hallmark of the verrucous phenotype. Beneath the parakeratotic layer, there is often a thinning of the granular layer and the suprapapillary plates, which is a feature commonly observed in psoriasis. However, VP also displays focal spongiosis, indicative of intercellular edema, and a superficial perivascular inflammatory infiltrate that may contain a mixture of lymphocytes and neutrophils. The presence of Munro's microabscesses and spongiform pustules of Kogoj, while not invariant, adds to the histologic diagnosis when observed. The absence of koilocytic changes and the negative immunostaining or polymerase chain reaction for Human Papillomavirus (HPV) help to differentiate VP from verruca vulgaris and other HPV-related conditions. Furthermore, the histopathologic features of VP may show variations, reflecting the dynamic nature of the disease process and the potential influence of external factors such as trauma and inflammation.

The pathogenesis of VP remains elusive, but is hypothesized to involve factors such as repeated trauma, lymphatic obstruction, microangiopathy, diabetes, and obesity. In the dermatologic literature, a series of case reports have shed light on the intriguing phenomenon of VP, which may be associated with various comorbidities. Sanyal et al., described a case of unilateral VP emerging after coronary artery bypass surgery [2]. Baba et al., presented a case of psoriasis with verrucous appearance, suggesting a potential link between local lymphatic abnormalities and the development of such lesions [8]. Savoia et al., described a case of Elephantiasis Nostras Verrucosa (ENV) co-occurring with psoriasis, proposing a multifactorial pathogenesis involving chronic venous insufficiency, obesity, and congestive heart failure, and responding to a comprehensive treatment approach [9]. The simultaneous occurrence of VP, along with the aforementioned conditions, suggests a multifactorial etiology. These comorbidities may induce microenvironmental changes that predispose to the verrucous transformation of psoriatic lesions. Besides, the potential exacerbating role of interferon therapy in hepatitis C patients developing VP and emergence of VP post secukinumab therapy, underscores the influence of systemic treatments on cutaneous manifestations. These cases collectively suggest a complex interplay between local tissue alterations, systemic conditions, and therapeutic interventions in the pathogenesis of VP [10,11].

The discourse on the therapeutics of VP has evolved, with an emerging body of literature underscoring the heterogeneity in treatment responses and the exploration of novel biologic agents. Traditional therapeutics, such as topical corticosteroids, methotrexate, and acitretin, have demonstrated variable efficacy, with some cases illustrating successful outcomes, as reported by Moesch et al., with topical steroids and Shivers and Montanez- Wiscovich with methotrexate and acitretin combination therapy [12-13].

Notably, Kenya Wakamatsu et al., emphasized the role of oral etretinate and compression bandaging in achieving remission, highlighting the necessity for tailored treatment strategies. In the realm of biological therapy, a paradigm shift has occurred, with an array of case reports attesting to the remarkable responses observed with agents targeting specific immune pathways. Duarte et al., showcased the therapeutic potential of adalimumab, an anti- Tumor Necrosis Factor-Alpha (TNF-α) agent, in a case of unilateral VP [14,15]. Similarly Maejima et al., reported the efficacy of adalimumab, reinforcing the significance of TNF-α inhibition in recalcitrant VP [16].

Apremilast, a phosphodiesterase 4 inhibitor, has also garnered attention, with successful treatment reports by Xenopoulou et al., Okazaki et al., suggesting its utility in refractory cases. The advent of Interleukin-17A (IL-17A) inhibition has further expanded the therapeutic arsenal, with ixekizumab demonstrating efficacy in both adult and pediatric populations, as illustrated by Sherkin et al., [17-19]. The discontinuation of ustekinumab, an IL-12/23 inhibitor, has been linked to the emergence of VP, as reported by Ger et al., [20]. However, Guo et al. delineates the emergence of VP in a patient following secukinumab therapy for psoriasis vulgaris, which was relieved by combination therapy of oral etretinate and ustekinumab following the standard regimen [11]. All of these reports underscored the intricate relationship between biologic therapy and atypical psoriasis presentations.

Discussion

VP, a rare and clinically distinct variant of psoriasis, presents with pronounced epidermal hyperplasia and a complex interplay of cellular, molecular, and signaling pathways. The pathophysiological underpinnings of VP are posited to involve an intricate interplay of cytokines, growth factors, and signaling cascades that collectively dictate the epidermal proliferative response. The dysregulation of this network, potentially instigated by genetic predispositions, immunological perturbations, or environmental triggers, culminates in the exaggerated hyperkeratotic phenotype characteristic of verrucous lesions.

The convergence of these case reports on the theme of VP in the context of various comorbidities enriches our understanding of the disease's pathophysiology. It also emphasizes the necessity for clinicians to maintain a high index of suspicion for atypical presentations of psoriasis, particularly in patients with underlying systemic disorders or undergoing specific treatments, to ensure timely and effective intervention.

The heterogeneity in therapeutic response observed in VP may be attributed to the disruption of a delicate balance within a sophisticated network of regulatory factors that govern keratinocyte proliferation and differentiation. Given the multifactorial nature of epidermal hyperplasia regulation, it is plausible that a one-size- fits-all therapeutic approach may not be efficacious across the patient spectrum.

The variability in treatment outcomes suggests that the perturbed inflammatory milieu in VP may not uniformly respond to a single modality of intervention. However, the condition's embedment within the broader inflammatory framework implies that alternative anti-inflammatory therapies, customised to the specific derangements present, may yield superior outcomes. The therapeutic heterogeneity observed in VP highlights the need for a personalized medicine approach, wherein treatment strategies are informed by a comprehensive understanding of the molecular aberrations underpinning each case. Future research endeavors should focus on delineating the specific cytokine and signaling pathway imbalances in VP to identify novel therapeutic targets and biomarkers that predict treatment response. Moreover, the exploration of combinatorial therapeutic regimens that address the multifactorial aspects of VP may offer a more efficacious approach to management. The potential synergistic effects of combining targeted biological agents with traditional systemic therapies warrant investigation to enhance the therapeutic armamentarium against this recalcitrant dermatosis.

The treatment of VP is confounded by its complex pathophysiology and the heterogeneity of patient responses. The therapeutic landscape for VP is diversifying, with a convergence of evidence supporting the role of both traditional and biological agents. A deeper understanding of the cellular and molecular mechanisms driving this condition is imperative to develop more effective, personalized treatment strategies. The prospect of harnessing the complexity of the inflammatory network in VP to inform precision therapeutics holds promise for improving clinical outcomes in this challenging subset of patients.

The heterogeneity in treatment responses underscores the need for individualized therapeutic approaches and continued exploration of novel agents. The emergence of VP following biologic therapy or discontinuation highlights the complexity of disease management and the potential for immunologic rebound phenomena. As our understanding of VP's pathophysiology deepens, so too will the precision of our therapeutic interventions, ultimately enhancing the dermatologic care for patients afflicted with this rare and challenging variant of psoriasis.

Conclusion

VP represents a rare and therapeutically challenging variant of psoriasis. Its diagnosis relies on a combination of clinical suspicion, histopathological examination, and exclusion of other conditions with similar presentation. While traditional treatments offer limited benefits, the use of systemic therapies and biological agents has shown potential. Further research is warranted to better understand the pathogenesis of VP and to develop targeted treatment strategies.

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